Multiple oral doses of diazepam, oxazepam and phenobarbital to dogs--behavioural effects and correlation with antipyrine half-life

The effects of prolonged treatment with phenobarbital, diazepam, and oxazepam on behaviour and on the plasma half-life of antipyrine have been studied in the dog. In this species the biotransformation of diazepam and oxazepam is known to be very similar to man. After equipotent doses of phenobarbital (25 mg/kg) and diazepam (35 mg/kg), antipyrine half-life was found to decrease 80 and 40%, respectively, while after treatment with oxazepam (150 mg/kg) there was an increase of 20%. The behavioural effects declined in the dogs during the course of treatment with diazepam but were rather constant during treatment with oxazepam.